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1
Thomson, Laura Margaret. "Adrenomedullin, PAMP and adrenocortical function." Thesis, Queen Mary, University of London, 2001. http://qmro.qmul.ac.uk/xmlui/handle/123456789/25124.
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Adrenomedullin (AM) and pro-adrenomedullin N-terminal 20-peptide (PAMP) are peptides recently identified from a rat pheochromocytoma. Both of these peptides are cleavage products of pre-pro-AM. Specific receptors for AM have been characterised in several species, including rat and human. The aim of this study was to investigate the role of PAMP and AM in the adrenal cortex. Using an intact rat capsule preparation PAMP was shown to cause a dosedependent increase in aldosterone secretion, which was accompanied by a dosedependent increase in cAMP release. The effects of PAMP were inhibited by HA1004, an inhibitor of protein kinase A. These results suggest that PAMP stimulates aldosterone secretion from the zona glomerulosa via cAMP. Ligandbinding studies were then used to demonstrate the presence of specific PAMP receptors. Two classes of receptor were shown in the rat zona glomerulosa (Kdi 1.9 nmol/l, Bmai, 53 fmol/mg protein; Kd2 10 nmol/l, Bmac,2 225 fmol/mg protein). At the latter receptor PAMP was displaced by AM. None of the other competitors tested displaced PAMP. Using the H295R cell line, both PAMP and AM were shown to increase aldosterones ecretion in a dose-dependenmt anner. In both casesa corresponding dose-dependent increase in cAMP was observed. Both PAMP and AM also effected a dose dependent increase in cortisol secretion. mRNA analysis showed that the gene encoding pre-pro-AM was expressed in these cells. Immunocytochemistry confirmed that these cells were producing both PAMP and AM. Immunocytochemistry and mRNA analysis also revealed that both of the candidate receptors for AM, L1 and CRLR, are expressed in this cell line. Taken together these findings demonstrate that both AM and PAMP are produced by adrenocortical cells and likely to have a role in regulating adrenal steroidogenesis. Furthermore, these studies suggest the presence of a specific PAMP receptor in the rat adrenal gland.
2
Lloyd, Simon. "Mapping PAMP responses and disease resistance in brassicas." Thesis, University of East Anglia, 2014. https://ueaeprints.uea.ac.uk/49479/.
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The first layer of active defence in plants is based on the perception of pathogen-associated molecular patterns (PAMPs) leading to PAMP-triggered immunity (PTI). PTI is increasingly being investigated in crop plants, where it may have potential to provide durable disease resistance in the field. Limiting this work, however, is an absence of reliable bioassays to investigate PAMP responses in some species. Presented here is a series of methods to investigate PTI in Brassica napus. The assays allow measuring early cell signalling responses, gene expression changes, cell wall reinforcement, metabolome changes and scoring PAMP-Induced resistance. Illumina-based RNA sequencing analysis produced a genome-wide survey of transcriptional changes upon PAMP treatment seen in both the A and C genomes of the allotetraploid B. napus. Using these assays substantial variation in PAMP-responsiveness was observed amongst elite varieties of B. napus. Taking this further, a genome wide association study (GWAS) of the flg22 and elf18 triggered oxidative bursts, resistance to Pseudomonas syringae and Botrytis cinerea was carried out in a population of B. napus. A substantial number of molecular markers, covering both sequence and expression variation, have been identified as having significant association with these four traits. QTL mapping of the flg22 triggered oxidative burst in the ADxGD double haploid cross identified a major quantitative trait loci (QTL) on C9 of B. oleracea. mRNA-seq of the parents led to a non-synonymous single nucleotide polymorphism (SNP) list and enabled fine mapping through the addition of KASPar markers to the original map. This produced a relatively small list of candidate genes including CYLIC NUCLEOTIDE GATED ION CHANNEL 4 (CNGC4) also known as DEFENCE NO DEATH 2 (DND2). An insertion in Arabidopsis thaliana DND2 showed phenotypic difference in the oxidative burst between the insertion line and Col-0, potentially indicating a role for the gene in regulating early PTI.
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Niebergall, Roda. "Characterisation of potential regulators of PAMP-triggered immunity." Thesis, University of East Anglia, 2012. https://ueaeprints.uea.ac.uk/42367/.
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An essential part of plant innate immunity is the perception of pathogen-associated molecular patterns (PAMPs) through surface-localised pattern-recognition receptors (PRRs). EFR and FLS2 are well characterised PRRs, which recognise the bacterial elongation factor Tu and flagellin, respectively. A variety of downstream responses upon PAMP perception have been described. However, it is still poorly understood how EFR- and FLS2-dependent signalling is mediated. Here, I used two different approaches in order to identify novel components of both signalling pathways. First, I characterised seven candidate genes of a predicted flagellin-dependent gene expression network, which are predicted to regulate each other’s expression in a flagellin-dependent manner, and therefore, are potentially involved in the FLS2 signalling pathway. Further characterisation revealed that mutation of at least three of the seven candidate genes was affecting flg22-mediated signalling. In addition, I characterised a predicted protein phosphatase 2C (PP2C), which had been identified in a yeast two-hybrid screen with the EFR cytoplasmic domain and was therefore referred to as PIE (PP2C-interacting with EFR). Using Co-IP experiments, I confirmed that PIE associates with EFR in planta. Furthermore, PIE also associates with FLS2 and BIK1, a co-regulator of both PRRs, in planta. Interestingly, PIE dissociates from both the EFR and FLS2 complexes upon PAMP perception. PIE expressed in planta and in E. coli exhibits protein phosphatase activity and we showed that PIE dephosphorylates EFR, FLS2 and BIK1 in vitro. As expected from bio-informatic predictions, I confirmed that PIE is phosphorylated upon PAMP perception. Furthermore, I demonstrated that EFR and FLS2 kinase activities are partially required for PIE phosphorylation. Both PIE overexpression and pie knock-down lines display reduced PAMP-triggered responses, indicating that an optimal PIE expression level is required for proper induction of signalling. All together, these results imply that PIE is a novel regulator of the EFR and FLS2 signalling pathway.
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Masini, Laura. "Investigation of the molecular basis of PAMP-induced resistance." Thesis, University of East Anglia, 2014. https://ueaeprints.uea.ac.uk/58753/.
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The recognition of conserved microbial features termed pathogen-associated molecular patterns (PAMPs) by surface-localized pattern-recognition receptors (PRRs) constitutes the first layer of plant innate immunity. Although details of early immune signaling events are starting to be unveiled, the molecular mechanisms leading to restriction of pathogen growth are still poorly understood. To gain more insight into this process, two different approaches were employed. I used reverse genetics to study the involvement of three different secondary metabolites, namely camalexin, glucosinolates and callose, in PAMP-triggered immunity (PTI) against the phytopathogenic bacterium Pseudomonas syringae pv. tomato (Pto) DC3000. These are well known active defences Arabidopsis employs to restrict fungi and oomycetes invasion. Results showed that these compounds are dispensable for antibacterial resistance triggered by the bacterial PAMP flagellin (flg22). In addition, as an unbiased approach, I performed a novel genetic screen aimed at identifying molecular components required for induced resistance to Pto DC3000. For this, I developed a high-throughput assay for bacterial infection in Arabidopsis seedlings that enabled to select mutants impaired in flg22-induced resistance to Pto DC3000. The pir (PAMP-induced resistance) screen identified four loci whose mutation leads to a reproducible reduction of flg22-induced resistance. These genes have not been previously characterized for their role in immunity, and therefore can be considered as novel components of PTI. By employing a combination of reverse genetics, metabolomics and chemistry approaches, I obtained preliminary data suggesting that flavonoids act as cellular buffers and/or are employed as active defenses against bacteria. In addition, interference with the mevalonic acid biosynthetic pathway impairs antibacterial defenses, suggesting a role in immunity. Additional tests are underway to better assess the contribution of these PIR genes to PTI. Therefore, through the pir screen, I have identified several novel loci required for plant immunity that will increase our knowledge of the plant immune system.
5
Nitta, Yukino. "Regulation of plant defense responses downstream of PAMP receptors." Thesis, University of British Columbia, 2014. http://hdl.handle.net/2429/51596.
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Nativel, Brice. "Pathologie inflammatoire : étude de la contribution des PAMP et DAMP." Thesis, La Réunion, 2017. http://www.theses.fr/2017LARE0065.
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L’inflammation est le mécanisme de base du système immunitaire. Dans le cas de pathologie inflammatoire cette inflammation persiste et devient délétère pour l’organisme. Les causes de cette persistance peuvent être variées. L’une de ces causes est la présence de molécules induisant l’inflammation. Elles peuvent être d’origine exogène comme les PAMP (Pathogen-Associated Molecular Pattern). Ce sont des molécules issues des pathogènes (LPS, peptidoglycanes, ADN CpG) capables d’activer le système immunitaire. Ces molécules peuvent également être d’origine endogène comme les DAMP (Damage Associated Molecular Pattern). Ce sont des molécules libérées par les cellules en état de danger (HMGB1, HSP60) pour prévenir et activer le système immunitaire. La présence de récepteurs (TLR2, TLR4, RAGE) capable de reconnaitre ces PAMP et DAMP est également nécessaire pour pouvoir induire une inflammation. Mes travaux explorent les mécanismes moléculaires et cellulaires des PAMP et des DAMP, dans l’installation et le maintien de l’inflammation dans le cadre des maladies inflammatoires. Pour cela mon étude se focalise sur les mécanismes de reconnaissance et d’induction de l’inflammation par les PAMP et DAMP. Nous avons ainsi mis en évidence certains mécanismes cellulaires et moléculaires dans la réponse inflammatoire liés aux DAMP et PAMP. Nous nous sommes également intéressé aux récepteurs impliqués dans ces différents mécanismes et avons même mis en évidence un potentiel nouveau récepteur CD93. Nous émettons l’hypothèse que CD93 pourrait avoir un rôle dans les pathologies inflammatoires par cette capacité à lier les DAMP et PAMPInflammation is the basic mechanism of the immune system. In the case of inflammatory pathologies this inflammation persists and becomes deleterious to the organism. Many reasons can explain this persistance. One of these causes is the presence of inflammatory-inducing molecules. They may have exogenous origin such as PAMP (Pathogen Associated Molecular Pattern). They are derived from pathogens (LPS, peptidoglycans, CpG DNA ...), and are able to activate the immune system. These molecules can also have endogenous origin such as the DAMP (Damage Associated Molecular Pattern). They are released by stress cells (HMGB1, HSP60, S100 ...) to prevent and activate the immune system. The presence of receptors (TLR2, TLR4, RAGE ...) capable of recognizing these PAMPs and DAMPs is also necessary in order to elicit inflammation.My work explores the contribution of PAMPs and DAMPs to inflammatory diseases at molecular and cellular levels. To this end, my study focuses on recognition and induction of inflammation by PAMPs and DAMPs.We have thus demonstrated cellular and molecular mechanisms in the inflammatory response related to DAMP and PAMP. We were also interested in the receptors involved in these mechanisms and even showed a new potential receptor. We hypothesize that CD93 may have a role in inflammatory pathologies by his ability to bind DAMPs and PAMPs. Thus CD93, HMGB1, HSP60 and LPS could be potential therapeutic targets concerning inflammatory diseases
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Schwessinger, Benjamin. "Genetic analysis of signalling components of PAMP-triggered immunity (PTI) in plants." Thesis, University of East Anglia, 2010. https://ueaeprints.uea.ac.uk/25632/.
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Rallapalli, Ghanasyam. "Sequencing based expression profiling to dissect transcriptional regulation during PAMP-triggered immunity." Thesis, University of East Anglia, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.539357.
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Gäbler, Yvonne. "Identifizierung und Charakterisierung von PAMP-induzierbaren Genen in Petroselinum crispum und Arabidopsis thaliana." [S.l. : s.n.], 2007.
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Doñate, Jimeno Carmen. "A transcriptomic approach toward understanding PAMP-driven macrophage activation and dietary immunostimulation in fish." Doctoral thesis, Universitat Autònoma de Barcelona, 2008. http://hdl.handle.net/10803/3816.
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Los peces son claramente el grupo más exitoso y diverso de vertebrados, representando el 40% de todas las especies de vertebrados y mostrando un impresionante nivel de diversidad en distintos aspectos biológicos. Exhiben un gran número de particularidades genómicas únicas entre los vertebrados, que presentan a los peces como un modelo muy interesante para diversas disciplinas, en particular aquellas relacionas con la evolución. Por estas razones, algunas especies de peces han tenido un papel muy importante en los últimos años en el incremento del conocimiento de la especialización del genoma en vertebrados. Por otra parte, tienen una importancia vital como comida, siendo la acuicultura un sector productor alimentario esencial en todo el mundo. El objetivo del presente trabajo ha sido caracterizar ciertos aspectos moleculares y funcionales del sistema inmune de dos especies distantes en la evolución, Sparus aurata (dorada) y Oncorhynchus mykiss (trucha arco iris), con especial énfasis en sus respuestas transcriptómicas a diferentes estímulos relativos a patógenos. Con esta finalidad, análisis in vivo e in vitro fueron combinados para evaluar mecanismos inmunitarios globales de estos teleósteos. Los Macrófagos representan un grupo importante de células que poseen un papel principal en la iniciación y coordinación de la respuesta inmune. Se desarrolló y caracterizó un cultivo primario de macrófagos diferenciados in vitro de dorada, investigando aspectos como morfología, capacidad fagocítica y respuesta a lipopolisacárido (LPS) de este tipo celular. En paralelo, CD83, una proteína de membrana utilizada como marcador estándar de células dendríticas en mamíferos fue clonada y analizada usando Q-PCR (PCR a tiempo real, cuantitativa). A continuación, los macrófagos diferenciados de dorada fueron comparados con los de trucha, evaluando sus diferencias en la activación de vías antivirales bajo la inducción de LPS y las implicaciones de la presencia de contaminantes en preparaciones comerciales de LPS. La expresión de varios genes antivirales fue cuantificada mediante Q-PCR. Para analizar más profundamente las respuestas inmunes de macrófagos, su regulación transcriptómica en respuesta a LPS bacteriano y Poly (I:C) viral fue estudiada utilizando una plataforma de microarray de cDNA enriquecida en genes con funciones inmunes, resultados que fueron posteriormente validados con Q-PCR, junto con el análisis mediante western blot de la liberación de la citoquina inflamatoria Factor de Necrosis Tumoral α (TNFα). Finalmente, la regulación de cortisol y la respuesta trancriptómica de los teleósteos a una modulación inmune fue evaluada a través de la administración de dietas inmunoestimulantes, que son comúnmente utilizadas en acuicultura. A través de diversos análisis, utilizando la plataforma de microarray, hibridaciones in situ y cuantificación de los niveles de cortisol en plasma por R.I.A., estudiamos respuestas específicas en tejidos (riñón anterior, bazo, intestino y branquias) en truchas alimentadas durante cuatro semanas con una dieta inmunoestimulante, en condicones basales y siguiendo una inducción con LPS. Los resultados obtenidos han sido presentados y discutidos en este trabajo.
Fish are by far the most successful and diverse group of vertebrates, representing 40% of all vertebrate species and displaying an amazing level of diversity in several biological aspects. They exhibit a number of genomic particularities unique among vertebrates that present fish as a very interesting model to gain an insight into a wide variety of disciplines, in particular those related to evolution. Therefore some fish species have played important roles in the latest years to increase the knowledge of vertebrate genome speciation. On the other hand, they are of tremendous importance as food for people, becoming the aquaculture industry an essential food-producing sector all around the world. The goal of the present study has been to characterize several molecular and functional aspects of the immune system of two evolutionary distant fish species, Sparus aurata (gilthead sea bream) and Oncorhynchus mykiss (rainbow trout), with specific emphasis on their transcriptomic responses to different pathogen-related challenges. To that end, in vivo and in vitro analyses were combined to evaluate global immune mechanisms of these teleosts.
The macrophage cell lineage represents an important group of cells which play a central role in the initiation and coordination of the immune response. A primary culture of in vitro differentiated macrophages of gilthead sea bream was developed and characterized; therefore aspects as morphology, phagocytic capacity and response to lipopolysaccharides (LPS) of these cells were investigated. In parallel, CD83, a cell surface membrane used as standard surface marker for dendritic cells in mammals, was cloned and then analyzed from the gilthead sea bream macrophages using Q-PCR (real-time quantitative-PCR). Once this in vitro model was characterized and validated, differentiated macrophages of gilthead sea bream were compared with those of rainbow trout to evaluate their differences in the activation of antiviral-related pathways upon LPS induction and the implications of the presence of contaminants in commercial LPS preparations when analyzing regulation of gene expression. Expression of antiviral genes in macrophages stimulated with different LPS preparations were quantified with Q-PCR. To further address rainbow trout macrophages immune responses, their transcriptomic regulation in response to bacterial LPS and viral Poly I:C was studied using a salmonid-specific cDNA microarray platform enriched in immune-related genes and validated with Q-PCR, together with the analysis of the release of the pro-inflammatory cytokine tumor necrosis factor α (TNFα) by western blot. Finally, the cortisol regulation and transcriptomic response of teleost fish to immuno-modulation were investigated via the administration of immunostimulant diets, which are commonly utilized in aquaculture. Using the salmonid-specific microarray platform, in situ hybridizations and quantification of plasma cortisol levels by radioimmunoassay, we studied tissue specific (head kidney, spleen, intestine and gills) responses in rainbow trout fed for four weeks with a commercial immunostimulant diet, in a basal situation and following a challenge with LPS. The results obtained are presented and discussed in this report.
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Salina, Ana Carolina Guerta [UNESP]. "Eferocitose na presença de PAMP estimula ativação de macrófagos de perfil misto M1/M2." Universidade Estadual Paulista (UNESP), 2015. http://hdl.handle.net/11449/131978.
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000851662.pdf: 1696866 bytes, checksum: d81719395199b25212968ab82e23a88e (MD5)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
A fagocitose de células apoptóticas é um processo dinâmico importante para a homeostase dos tecidos após injúria. Os macrófagos além de atuarem na remoção de células apoptóticas, também colaboram na defesa contra microrganismos. Existem ao menos duas populações de macrófagos classificadas como macrófagos M1 (pró-inflamatórios) e macrófagos M2 (anti-inflamatórios). Estes leucócitos diferem quanto ao fenótipo e funções efetoras dependendo, primordialmente, do microambiente e dos microrganismos com que interagem no tecido. Em uma situação de injúria pulmonar estéril (inalação de agentes tóxicos), há acúmulo de células apoptóticas sem a presença de agente microbiano. Por outro lado, durante uma infecção pulmonar bacteriana, ocorre intensa migração de células para o local da infecção na tentativa de conter a proliferação bacteriana, resultando em intenso acúmulo de células apoptóticas infectadas neste tecido. Portanto, nesse trabalho foi avaliado, in vitro e in vivo, o efeito da fagocitose de células apoptóticas infectadas (AC-Sp) ou estéreis (AC) na polarização de macrófagos M1/M2, bem como suas funções efetoras, e o efeito da PGE2 nesse contexto de eferocitose. Macrófagos M0 co-cultivados com AC ou AC-Sp apresentam um fenótipo intermediário entre M1 e M2, com secreção de altos níveis de IL-6, TNF-α, PGE2, TGF-β e NO e a expressão de genes relacionados ao perfil M1, iNOS, e ao perfil M2, Arginase 1. Além disso, macrófagos M0 cultivados com AC ou AC-Sp, apresentam supressão da função microbicida quando desafiados com S. pneumoniae. A presença de PGE2 dirige a polarização de macrófagos M0 a um perfil M2 e a presença de inibidores de COX promove a reversão do fenótipo de polarização destes macrófagos. Os resultados in vivo demonstram que a instilação de AC ou AC-Sp promove distintos microambientes no pulmão destes animais, que influenciam na resolução da infecção.....
The phagocytosis of apoptotic cells is dynamic and crucial for homeostasis after injury. Macrophages act on the clearance of apoptotic cells and collaborate with defense against microorganisms. There are at least two distinct macrophage populations classified as M1 macrophages (pro-inflammatory) and M2 macrophages (anti-inflammatory). Both cells differ on the state of polarization and effectors function depending primarily on the microenvironment and microorganisms that interact into the tissue. In a situation of sterile lung injury (inhalation of toxic agents), there are accumulation of apoptotic cells without the presence of pathogen. On the other hand, during a bacterial pulmonary infection there is intense cell migration to the infection site in an attempt to impair bacterial growth, resulting in a large accumulation of infected-apoptotic cells in the tissue. Therefore, this study has evaluated in vitro and in vivo, the effect of the phagocytosis of infected-apoptotic cells (AC-Sp) or sterile cells (AC) on the polarization of M1/M2 macrophages, as well as in their effector functions and the effect of PGE2 in the context of efferocytosis. M0 macrophages co-cultured with AC or AC-Sp show an intermediate phenotype between M1 and M2 with high secretion levels of IL-6, TNF-α, PGE2, NO and TGF-β, and gene expression profile related to M1, iNOS, and M2, arginase 1. Furthermore, M0 macrophages cultured with AC or AC-Sp show strong suppression of the macrophage microbicidal function when challenged with S. pneumonia. The presence of PGE2 drives the polarization of M0 macrophages to a M2 profile, and in the presence of COX inhibitors, it reverses the polarization of this macrophage phenotype. The in vivo results demonstrate that the instillation of AC or AC-Sp promotes distinct microenvironments in the lungs of these animals, which influence the resolution of the infection. All these results suggest that the presence of AC or AC-Sp promotes, ...
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Salina, Ana Carolina Guerta. "Eferocitose na presença de PAMP estimula ativação de macrófagos de perfil misto M1/M2 /." Araraquara, 2015. http://hdl.handle.net/11449/131978.
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Orientador : Alexandra Ivo de MedeirosBanca: Vania Luiza Deperon Bonato
Banca: Carlos Rossa Junior
Resumo: A fagocitose de células apoptóticas é um processo dinâmico importante para a homeostase dos tecidos após injúria. Os macrófagos além de atuarem na remoção de células apoptóticas, também colaboram na defesa contra microrganismos. Existem ao menos duas populações de macrófagos classificadas como macrófagos M1 (pró-inflamatórios) e macrófagos M2 (anti-inflamatórios). Estes leucócitos diferem quanto ao fenótipo e funções efetoras dependendo, primordialmente, do microambiente e dos microrganismos com que interagem no tecido. Em uma situação de injúria pulmonar estéril (inalação de agentes tóxicos), há acúmulo de células apoptóticas sem a presença de agente microbiano. Por outro lado, durante uma infecção pulmonar bacteriana, ocorre intensa migração de células para o local da infecção na tentativa de conter a proliferação bacteriana, resultando em intenso acúmulo de células apoptóticas infectadas neste tecido. Portanto, nesse trabalho foi avaliado, in vitro e in vivo, o efeito da fagocitose de células apoptóticas infectadas (AC-Sp) ou estéreis (AC) na polarização de macrófagos M1/M2, bem como suas funções efetoras, e o efeito da PGE2 nesse contexto de eferocitose. Macrófagos M0 co-cultivados com AC ou AC-Sp apresentam um fenótipo intermediário entre M1 e M2, com secreção de altos níveis de IL-6, TNF-α, PGE2, TGF-β e NO e a expressão de genes relacionados ao perfil M1, iNOS, e ao perfil M2, Arginase 1. Além disso, macrófagos M0 cultivados com AC ou AC-Sp, apresentam supressão da função microbicida quando desafiados com S. pneumoniae. A presença de PGE2 dirige a polarização de macrófagos M0 a um perfil M2 e a presença de inibidores de COX promove a reversão do fenótipo de polarização destes macrófagos. Os resultados in vivo demonstram que a instilação de AC ou AC-Sp promove distintos microambientes no pulmão destes animais, que influenciam na resolução da infecção.....
Abstract: The phagocytosis of apoptotic cells is dynamic and crucial for homeostasis after injury. Macrophages act on the clearance of apoptotic cells and collaborate with defense against microorganisms. There are at least two distinct macrophage populations classified as M1 macrophages (pro-inflammatory) and M2 macrophages (anti-inflammatory). Both cells differ on the state of polarization and effectors function depending primarily on the microenvironment and microorganisms that interact into the tissue. In a situation of sterile lung injury (inhalation of toxic agents), there are accumulation of apoptotic cells without the presence of pathogen. On the other hand, during a bacterial pulmonary infection there is intense cell migration to the infection site in an attempt to impair bacterial growth, resulting in a large accumulation of infected-apoptotic cells in the tissue. Therefore, this study has evaluated in vitro and in vivo, the effect of the phagocytosis of infected-apoptotic cells (AC-Sp) or sterile cells (AC) on the polarization of M1/M2 macrophages, as well as in their effector functions and the effect of PGE2 in the context of efferocytosis. M0 macrophages co-cultured with AC or AC-Sp show an intermediate phenotype between M1 and M2 with high secretion levels of IL-6, TNF-α, PGE2, NO and TGF-β, and gene expression profile related to M1, iNOS, and M2, arginase 1. Furthermore, M0 macrophages cultured with AC or AC-Sp show strong suppression of the macrophage microbicidal function when challenged with S. pneumonia. The presence of PGE2 drives the polarization of M0 macrophages to a M2 profile, and in the presence of COX inhibitors, it reverses the polarization of this macrophage phenotype. The in vivo results demonstrate that the instillation of AC or AC-Sp promotes distinct microenvironments in the lungs of these animals, which influence the resolution of the infection. All these results suggest that the presence of AC or AC-Sp promotes, ...
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Lopes, Martin Rafaela. "Induction de la PAMP-Triggered Immunity par des éliciteurs d’origine différente chez Solanum tuberosum." Thesis, Rennes, Agrocampus Ouest, 2020. http://www.theses.fr/2020NSARC147.
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L’induction de réponses de défense via la Pathogen-Associated Molecular Pattern (PAMP)-Triggered Immunity fournit à toutes les plantes un arsenal de composés antimicrobiens contre les agents pathogènes. La stimulation de ces défenses par des éliciteurs exogènes serait une stratégie pour réduire les pesticides mais nécessite une meilleure compréhension des mécanismes de l’induction qui pourrait dépendre de l'éliciteur et du génotype. Deux génotypes de pomme de terre partiellement résistants à Phytophthora infestans ont été traités avec un PAMPs de P. infestans, un filtrat de culture concentré (CCF), une molécule synthétique, l’acide ß-aminobutyrique (BABA) et un extrait d’Ulva spp. Les métabolites induits dans les folioles, 48h plus tard, ont été comparés par une approche de métabolomique non ciblée (UPLC-qTOF-MSe) puis par des approches ciblées demétabolomique et transcriptomique. Les résultats ont montré que (i) chaque éliciteur induit une reprogrammation spécifique du métabolome confirmée partiellement par les transcrits : BABA et CCF ont induit les benzylisoquinoléine alcaloïdes et l'extrait d'Ulva, les stérols alcaloïdes et les phénylpropanoïdes; ii) la signalisation dépend de la voie du JA pour l’extrait d'Ulva, et de celle du SA pour BABA et CCF ; (iii) l’abondance de certains métabolites est génotype-dépendant. Nos résultats suggèrent que l’induction des composés antimicrobiens dépend de la perception spécifique de l’éliciteur et de l'interaction éliciteur/génotype. Afin d'améliorer leur efficacité sur le terrain, une attention particulière doit être portée à la siThe induction of response defences via the Pathogen-Associated Molecular Pattern (PAMP)-Triggered Immunity provides all plants an arsenal of antimicrobial compounds against pathogens. Stimulation of these defences by exogenous elicitors could be a strategy to reduce the pesticides but this requires a better understanding of the induction mechanisms. This induction could depend on both the origin of the elicitor and the genotype. Two potato genotypes partially resistant to Phytophthora infestans were treated with a PAMPs from P. infestans, the Concentrated Culture Filtrate (CCF), a synthetic molecule, the ß-aminobutyric acid (BABA); and an Ulva spp extract. 48h after treatment, the induced metabolites in the leaflets were first compared by a non target metabolomic using a UPLC-qTOF-MSe, then through targeted metabolomic and transcriptomic approaches.The results showed that (i) each elicitor induced a specific metabolic profile reprogramming, partially confirmed by transcript analysis: the BABA and the CCF induced the benzylisoquinoline alkaloids and the Ulva extract, the alkaloid sterols and phenylpropanoids; (ii) the signalling depended on the JA pathway for the Ulva extract while it is rather SA pathway-dependent for the BABA and CCF; (iii) the abundance of several antimicrobial metabolites was genotype-dependent. Our results suggest that the induction of the antimicrobial compounds depends on the elicitor/genotype interaction and on the specific perception of the elicitor. In order to improve their efficiency in the field, special attention should be paid on the defence
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Boltaña, Harms Sebastian. "Molecular characterisation of the underlying mechanisms of pathogen-associated molecular pattern (PAMP) recognition in fish." Doctoral thesis, Universitat Autònoma de Barcelona, 2011. http://hdl.handle.net/10803/42005.
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La respuesta inmune innata es basada en la activación de receptores
genotípicamente codificados, llamados receptores de reconocimiento de patógenos
(PRR). Los PRR pueden ser proteínas solubles tal como las proteínas plasmáticas
PGRPs o pueden estar anclados en las membranas celulares como los TLR. Estos
receptores son capaces de reconocer a los patógenos o a sus patrones moleculares
(PAMPs). La interacción PAMP-PRR provoca la activación de genes diana y
promueve la producción de mediadores pro- e inflamatorios. El principal objetivo
de esta tesis doctoral fue la caracterización de las respuestas de macrófagos de la
trucha arcoíris Oncorhynchus mykiss, y de la dorada tratados con diferentes
PAMPs y la subsecuente exploración de cambios en la expresión de genes
relacionados con la respuesta inmune así como cambios globales en la respuesta
transcriptómica de los macrófagos. Un objetivo especifico de este estudio fue
registrar los cambios en los macrófagos activados hacia un fenotipo inflamatorio
después de tratamientos con lipopolisacarido (LPS) crudo de bacterias Gram
negativas, enfatizando que el peptidoglicano (PGN) es un contaminante
encontrado en las preparaciones crudas de LPS. PGN es capaz de inducir la
expresión de mRNA de IL-1β y IL-6 e inducir la liberación de productos
inflamatorios como prostaglandinas. Los análisis de microarray fueron hechos
para describir la concentración y la dependencia en el tiempo de las modulaciones
transcriptómicas en los macrófagos de trucha y dorada tratados con PGN o LPS.
En el caso de dorada, se diseño y valido un microarray de oligonucleótidos. Los
resultados revelaron la sobre-regulación de transcritos específicos que están
cercanamente relacionados con la síntesis de prostaglandinas y las vías de
señalización activadas a partir de TLR. Así, el reconocimiento de PGN en peces
resulta del reconocimiento de mecanismos específicos que no incluyen TLR pero si
otros grupos de receptores como PGRPs o NODs. Estos mecanismos parecen ser
conservados en la respuesta de defensa innata a lo largo del grupo de los
vertebrados.The innate immune response is based upon the activation of a restricted number of genotypic encoded receptors, the pathogen recognition receptors (PRRs). PRRs can be soluble proteins such as plasmatic PGRPs or cell membraneanchored TLRs able to recognize pathogens or their pathogen-associated molecular patterns (PAMPs). PAMP-PRR interaction results in the activation of target genes and promotes the production of pro- and inflammatory mediators. The main goal of this dissertation was to characterise the responses of rainbow trout, Oncorhynchus mykiss, and gilthead seabream, Sparus aurata, macrophages treated with different PAMPs and to explore subsequent changes in the expression of immune related genes or global shifts in the macrophage transcriptome. A specific goal of this study was to register changes in macrophages activated toward an inflammatory phenotype after treatments with crude gram negative bacterial lipopolysaccharide (LPS) preparations, highlighting that peptidoglycan (PGN) is a contaminant within crude LPS. PGN is able to induce the mRNA expression of IL- 1β and IL-6 and release inflammatory products such as prostaglandins. Microarray analyses were made to describe concentration and time-dependent transcriptional modulations both in trout and seabream macrophages treated with PGN or LPS. In the case of sea bream, a specific oligonucleotide microarray was designed and validated for these studies. Results reveal up-regulation of specific mRNA transcripts that are closely related to prostaglandin synthesis and TLR signalling pathways. Thus PGN recognition in fish is a result of recognition mechanisms including non-TLR PRRs such as PGRPs and NODs. These mechanisms appear to be conserved throughout the vertebrate innate immune response.
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Pamp, Oliver [Verfasser]. "Political Preferences and the Aging of Populations : Political-Economy Explanations of Pension Reform / Oliver Pamp." Berlin : Freie Universität Berlin, 2013. http://d-nb.info/1043957790/34.
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Ben, Khaled Sara. "Post-translational events control pattern recognition receptor trafficking to preserve PAMP responsiveness in plant immunity." Thesis, University of East Anglia, 2016. https://ueaeprints.uea.ac.uk/61723/.
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Pattern recognition receptors (PRRs) are localized at the cell surface to recognize conserved microbial patterns and activate plant immunity. The activation status regulates the localization of ligand-bound PRRs and routing to late endocytic trafficking for vacuolar degradation. This ligand-induced endocytosis is conserved across PRR families, and best characterized for the receptor kinases flagellin-sensing 2 (FLS2) and EF-Tu receptor (EFR), both mediating anti-bacterial immunity. However, the molecular determinants of FLS2 and EFR endocytic trafficking, as well as the biological relevance of these processes remain poorly understood. In this study, I have dissectedlolo l the molecular code underlying ligand-mediated endocytosis. I show that flagellin induced the interaction of FLS2 with vacuolar protein sorting (VPS) 37-1, a subunit of the endosomal complex required for transport-I (ESCRT-I) that recognizes internalized ubiquitinated proteins for vacuolar sorting. This led me to investigate the role of ubiquitination in FLS2 endocytosis. Using mass-spectrometry and mutational approaches, I identified ubiquitinated FLS2 lysine residues potentially involved in FLS2 endocytic trafficking. Additionally, I revealed an involvement of the E3 ligases keep on going (KEG) and the two redundant plant U-box (PUB) 12 and PUB13 in FLS2 trafficking. I showed that PUB12/PUB13-mediated monoubiquitination of FLS2 is a key regulatory process for internalisation of activated receptors, while EFR endocytic degradation is regulated by receptor phosphorylation on the tyrosine residues 875 and 877. For both FLS2 and EFR, altering ligand-induced endocytosis did not impact the initiation of downstream signalling, demonstrating that these processes are uncoupled. Instead, my results showed that ligand-mediated endocytosis of FLS2 and EFR plays a pivotal role in maintaining chronic immune signalling responses upon long term ligand stimulation. Overall, my results uncover an important molecular mechanism regulating the subcellular trafficking of the central immune components FLS2 and EFR, and extend our understanding on how plant responsiveness to its surrounding pathogens is maintained.
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Lee, Min-Hi. "Induction and regulation of antiviral defence mechanisms through intracytoplasmic sensors." Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2009. http://dx.doi.org/10.18452/15950.
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Das Wechselspiel zwischen Viren und ihren Wirtszellen beginnt meist an pattern recognition-Rezeptoren (PRRs), die für die Erkennung unterschiedlichster Pathogene anhand bestimmter Strukturen, sogenannten pathogen-associated molecular patterns (PAMPs), zuständig sind. Nach Detektion lösen die PRRs über verschiedene Signalkaskaden eine antivirale Antwort aus, die zur Expression antiviraler Gene führt. RIG-I und MDA5 sind zytoplasmatisch lokalisierte PRRs und erkennen RNA-Strukturen, die insbesondere während der viralen Replikation und Transkription verfügbar sind. Hantaviren sind humanpathogene RNA-Viren mit einem einzelsträngigen, segmentierten Genom. Die Konsequenzen hantaviraler Infektionen auf molekularer Ebene wurden bereits detailliert untersucht, aber die Mechanismen, die zur Induktion der Immunantwort führen, wie auch mögliche Immunevasionsstrategien, die wahrscheinlich in Zusammenhang mit der Pathogenität des jeweiligen Hantavirusstamms variieren, konnten bisher nicht identifiziert werden. Da Hantaviren im Cytoplasma ihrer Wirtszellen replizieren, stellen RIG-I und MDA5 potentielle Detektoren dar. In dieser Doktorarbeit wird die Bedeutung von RIG-I und MDA5 für die Erkennung von Hantavirus-Infektionen untersucht. Wachstumskinetiken zeigten, daß RIG-I die Replikation von pathogenen wie auch apathogenen Hantaviren beeinträchtigt. Außerdem konnte die RNA hantaviraler Nukleocapsid- (N-) ORFs als eine virale Komponente identifiziert werden, die Typ I Interferon über RIG-I induziert. Das Ausmaß der Interferon-Aktivierung korrelierte hierbei tendenziell mit dem Virulenzgrad der Virusstämme und war für die nicht-pathogenen Hantaviren nicht nachweisbar. Unterschiede in der Aktivierungsstärke können anhand vorläufiger Daten wahrscheinlich auf noch nicht identifizierte Motive zurückgeführt werden, die am 3’-Ende der N ORFs liegen. Im Gegensatz dazu wurde keine Interferon-Aktivierung durch hantavirale Komponenten über MDA5 festgestellt.Host-virus interaction is usually initated by pattern recognition receptors (PRRs) which are responsible for the recognition of various pathogens based on so-called pathogen-associated molecular patterns (PAMPs). Upon detection, PRRs trigger an antiviral immune response through different signalling cascades that lead to the expression of antiviral genes including interferon genes. RIG-I and MDA5 are cytoplasmically localised PRRs and recognise RNA patterns that are particularly available during viral replication and transcription. Hantaviruses are RNA viruses with single-stranded segmented genomes. The consequences of hantaviral infections have been analysed in detail, but the mechanisms that lead to the induction of the innate immune response as well as immune evasion strategies depending on the pathogenicity of the respective hantavirus strains have not been identified yet. Since hantaviruses replicate in the cytoplasm of their host cells, RIG-I and MDA5 represent potential PRRs for hantaviral detection. This thesis investigates the impact of RIG-I and MDA5 on recognition of hantaviral infections. Growth kinetics show that RIG-I impairs the replication of pathogenic as well as non-pathogenic hantaviruses. Furthermore, the RNA of hantaviral nucleocapsid protein (N) ORF could be identified as a viral component responsible for the induction of RIG-I signalling. It is shown that the degree of interferon promotor activation correlates with the virulence of the hantavirus strain from which the N ORF was derived. Based on preliminary data, differences in activation strength may be attributed to not yet identified motifs at the 3’ end of the ORF. In contrast, no interferon activation through MDA5 could be observed.
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Thomas, Cécile. "Interactions entre résistance induite chez Solanum tuberosum et traits d’histoire de vie et effecteurs de Phytophthora infestans." Thesis, Rennes, Agrocampus Ouest, 2019. http://www.theses.fr/2019NSARC141/document.
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La gestion de Phytophthora infestans, agent du mildiou de la pomme de terre, nécessite l’application d’une quinzaine de traitements par saison culturale. Pour réduire l’usage des fongicides, combiner résistance induite et résistance quantitative pourrait être une bonne stratégie. Elle nécessite cependant une meilleure connaissance des interactions entre les réponses physiologiques de Solanum tuberosum et l’écologie de P. infestans. Dans cet objectif, les réponses de défense induites chez la pomme de terre ont été confrontées aux traits d’histoire de vie et effecteurs de P. infestans. Quatre génotypes présentant différents niveaux de résistance ont été traités avec un filtrat de culture concentré (CCF) de P. infestans induisant la PAMP-triggered immunity (PTI). Des folioles détachées ont ensuite été inoculées avec des souches rapides ou lentes de P. infestans. Les expressions de 14 gènes de défense et de 6 effecteurs ont été analysée simultanément par qRT-PCR.Les symptômes de la maladie ont été mesurés classiquement ou par analyse d’images dans le visible et en fluorescence. Les résultats obtenus montrent que la réduction des symptômes après induction de la PTI est fonction du couple génotype-souche. En effet, l’efficacité des défenses induites par le CCF dépend des stratégies d’échappement (vitesse de croissance) ou d’adaptation (effecteurs) de P. infestans et du potentiel d’inductibilité du génotype (expression des protéines PR). Ainsi, pour optimiser l’utilisation de la résistante induite il serait nécessaire de sélectionner des génotypes inductibles et capables de moduThe management of Phytophthora infestans, responsible for potato late blight, requires the application of about 15 fungicide treatments per cropping season. To reduce the use of pesticides, combining induced resistance and quantitative resistance could be a positive strategy. However, this method requires a better understanding of the interactions between Solanum tuberosum physiological responses and P. infestans ecology. To this end, defense responses induced in potato have been opposed to the pathogen life history traits and effectors. Four potato genotypes with different resistance levels were treated with a concentrated culture filtrate (CCF) of P. infestans inducing PAMPtriggered immunity (PTI). Then, detached leaflets were inoculated with fast- or slow-growing strains of P. infestans.The expression of 14 defense genes and the expression of 6 effectors were analyzed simultaneously by qRT-PCR. Disease symptoms were measured either conventionally or by visible and fluorescence image analysis. The results obtained show that the reduction of symptoms after induction of PTI was specific to the genotype-strain pair. Indeed, the effectiveness of induced defenses by CCF depends on either the escape (growth rate) or adaptation (effectors) strategies of P. infestans and on the genotype inductibility potential (expression of PR proteins). Thus, to optimize the use of induced resistance, it would be necessary to breed inducible genotypes that are able to modulate strains growth rate
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Landgraf, Ramona [Verfasser], Dierk [Akademischer Betreuer] Scheel, Holger [Akademischer Betreuer] Deising, and Christine [Akademischer Betreuer] Nawrath. "Charakterisierung des PAMP-induzierbaren Transporters ABCG1 aus Solanum tuberosum / Ramona Landgraf ; Dierk Scheel, Holger Deising, Christine Nawrath." Halle, 2016. http://d-nb.info/1120409985/34.
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Eliasse, Yoan. "L’acné : une mésentente entre P.acnes et le système immunitaire ?" Thesis, Toulouse 3, 2019. http://www.theses.fr/2019TOU30081.
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L’acné vulgaris est une maladie inflammatoire chronique affectant l’unité pilosébacée. Elle démarre le plus souvent à l’adolescence et résulte en des lésions pouvant être inflammatoires (papules, nodules) ou non inflammatoires (comédons ouverts ou fermés). Cette pathologie a fait l’objet de nombreuses études et quatre facteurs majeurs ont été décrits : une hyperkératinisation, un excès de la production de sébum, la mise en place d’une réponse inflammatoire et la colonisation du follicule pileux par la bactérie Propionibacterium acnes. Ce dernier point est l’un des plus débattu et le rôle de cette bactérie dans la pathologie reste encore mal compris, en particulier son interaction avec le système immunitaire. En effet, cette bactérie supposée commensale est suspectée d’être reconnue comme un pathogène dans le contexte de l’acné. L’objectif principal de mes travaux de thèse était de mieux comprendre le la perception de P.acnes par le système immunitaire. Pour cela nous avons tout d’abord établi une caractérisation phénotypique et fonctionnelle des cellules immunitaires présentes dès les premiers stades de l’apparition de la lésion (microkyste et papule), à partir de biopsies de la peau de patients acnéiques. Nous avons utilisé deux méthodes complémentaires : la cytométrie en flux et la microscopie confocale. Nos résultats indiquent un recrutement important des populations lymphocytaires Th17, des cellules dendritiques conventionnelles de type 2 (cDC2) et des mastocytes, mais également leurs activations à un stade très précoce. Nous avons ensuite observé in vivo la localisation et les interactions de ces populations par microscopie confocale et avons pu mettre en évidence la présence de mastocytes producteurs d’IL-17. Cette étude sur des biopsies de patients nous a permis de montrer l'implication des mastocytes dans l'acné et nous a conduits à étudier in vitro les mécanismes biologiques sous-jacents. Nous avons donc mis en place des modèles basés sur l’isolation et la culture de mastocytes primaires dans le but d’étudier les interactions avec P.acnes et les mécanismes impliqués dans la production d'IL-17 par les mastocytes. Dans un second axe de recherche, nous avons étudié l’impact d’une eau thermale sur des cellules dendritiques humaines. Nos résultats montrent que cette eau thermale réduit l’expression des marqueurs de différenciation et de maturation des cellules dendritiques après qu’elles aient été stimulées. En conclusion, mon travail de thèse nous a permis de découvrir l’implication des mastocytes dans la pathogénèse de l’acné comme source importante d’IL-17 aux stades précoces (microkyste et papule) de la formation de la lésion acnéiqueAcne vulgaris is a chronic inflammatory disease affecting the pilosebaceous unit. It usually begins in adolescence and results in lesions that can be inflammatory (papules, nodules) or non-inflammatory (open or closed comedones). This condition has been the topic of many studies and four major factors have been described: hyperkeratinization, excessive sebum production, the development of an inflammatory response and colonization of the hair follicle by the bacteria Propionibacterium acnes. This last point is one of the most debated and the role of this bacterium in the pathology is still poorly understood, especially concerning the role played by immune response. Indeed, this supposedly commensal bacterium is suspected of being recognized as a pathogen in the context of acne. The main objective of my thesis work was to better understand the "dialogue" established between the immune system and P.acnes. To do this, we first established a phenotypic and functional characterization of the immune cells present at the early stages of the lesion's development (microcyst and papule), based on skin biopsies of acne patients. We used two different but complementary methods: flow cytometry and confocal microscopy. Our results indicate a significant recruitment of Th17 lymphocyte populations, conventional dendritic cells 2 (cDC2) and mast cells, but also their activation at a very early stage. We then observed in vivo the localization of these cells and their interactions by confocal microscopy. This analysis allowed us to highlight the presence of mast cells producing IL-17. This study on patients’ biopsies revealed the involvement of mast cells in acne and led us to study in vitro the underlying biological mechanisms. We therefore set up models based on primary mast cell isolation and culture to study interactions with P.acnes and the mechanisms involved in the production of IL-17 by mast cells. In a second research axis, we studied the impact of spring thermal water on human dendritic cells. Our results show that this thermal water reduces the expression of markers of differentiation and maturation of dendritic cells after they have been stimulated. In conclusion, my thesis work led to the discovery of mast cells' involvement in acne pathogenesis as an important source of IL-17 in the early stages (microcyst and papule) of acne lesion formation
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Stegmann, Martin [Verfasser], Martin [Gutachter] Mueller, and Dirk [Gutachter] Becker. "Identification of PUB22 Targets and Functional Characterization in PAMP-Triggered Immunity / Martin Stegmann. Gutachter: Martin Mueller ; Dirk Becker." Würzburg : Universität Würzburg, 2013. http://d-nb.info/1102823074/34.
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Liu, Changxin. "Involvement of Polyamines in PAMP-triggered Immunity and Systemic Acquired Resistance (SAR). Extragenic Suppressors of Immune Hybrid Incompatibility." Doctoral thesis, Universitat de Barcelona, 2020. http://hdl.handle.net/10803/671759.
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The main topic of this Thesis is to investigate the contribution of polyamines to defense in Arabidopsis thaliana and the requirement of callose deposition for full expression of effector-triggered immunity in autoimmune hybrids. Due to its accumulation during pathogen infection, I mainly focused on the polyamine putrescine. The interaction between polyamines, reactive oxygen species (ROS) production and salicylic acid pathway activation is also studied in the context of PAMP-triggered immunity (PTI) (Chapter 1) and systemic acquired resistance (SAR) (Chapter 2). The data support a role for putrescine as a priming agent contributing to resistance against pathogens, which can lead to practical applications in the development of PPP (plant protection products). In Chapter 3, I report the involvement of glucan synthase-like 2 and 10 (GSL2 and GSL10), two of the twelve callose biosynthesis genes, in the temperature-dependent immune hybrid incompatibility between natural accessions of Arabidopsis thaliana from North Europe (Ler) and Central Asia (Kas-2), which constitutes a model for the study of effector-triggered immunity (ETI). This work supports that PTI and ETI are not two separate branches of defense, but support each other through mutual potentiation.
Overall, we provide evidence for the involvement of polyamines in defense signaling and callose biosynthesis in the establishment of ETI.
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Nur, Sabrina Ahmad Azmi. "Studies on an effector NLP1 expressed during the late phase of plant infection by Colletotrichum orbiculare." Kyoto University, 2018. http://hdl.handle.net/2433/233850.
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Kyoto University (京都大学)0048
新制・課程博士
博士(農学)
甲第21311号
農博第2296号
新制||農||1064(附属図書館)
学位論文||H30||N5145(農学部図書室)
京都大学大学院農学研究科応用生物科学専攻
(主査)教授 髙野 義孝, 教授 田中 千尋, 教授 寺内 良平
学位規則第4条第1項該当
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Fan, Li [Verfasser], and Thorsten [Akademischer Betreuer] Nürnberger. "Identification of a novel receptor of bacterial PAMP RsE in Arabidopsis using genomic tools / Li Fan ; Betreuer: Thorsten Nürnberger." Tübingen : Universitätsbibliothek Tübingen, 2016. http://d-nb.info/1197694501/34.
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Jäntsch, Christiane [Verfasser]. "Molekulare und physiologische Charakterisierung der Wirkung des Phytophthora infestans RXLR-Effektors PiAVR2 auf PAMP- und BR-Signalwege / Christiane Jäntsch." Tübingen : Universitätsbibliothek Tübingen, 2021. http://d-nb.info/1236994159/34.
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Plante, Audrey. "La maturation des cellules dendritiques induite par les PAMP modifie leur habileté à transférer le VIH-1 aux lymphocytes T CD4 + quiescents." Thesis, Université Laval, 2010. http://www.theses.ulaval.ca/2010/27664/27664.pdf.
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Böhm, Hannah Undine [Verfasser], and Thorsten [Akademischer Betreuer] Nürnberger. "Identification and characterization of a novel PAMP from a widespread microbial virulence factor and its perception system in Arabidopsis / Hannah Undine Böhm ; Betreuer: Thorsten Nürnberger." Tübingen : Universitätsbibliothek Tübingen, 2016. http://d-nb.info/119769465X/34.
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Böhm, Hannah [Verfasser], and Thorsten [Akademischer Betreuer] Nürnberger. "Identification and characterization of a novel PAMP from a widespread microbial virulence factor and its perception system in Arabidopsis / Hannah Undine Böhm ; Betreuer: Thorsten Nürnberger." Tübingen : Universitätsbibliothek Tübingen, 2016. http://d-nb.info/119769465X/34.
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Head, Debra K. "Urinary Excretion of (1-3)-Beta-D-Glucans." Digital Commons @ East Tennessee State University, 2008. https://dc.etsu.edu/etd/2002.
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(1→3)-β-D-Glucans are carbohydrate polymers that are present in the cell wall of various fungi and bacteria; they are pathogen associated molecular patterns that circulate during infection and modulate immunity. Our laboratory has previously established the pharmacokinetics of intravenously and orally administered glucans; the present studies investigated the renal excretion of (1→3)-β-D-glucans following intravenous and oral administration. Three fluorescently-labeled glucans were administered to adult male rats in the presence or absence of toxic challenge. Urine specimens were collected and analyzed by fluorescence spectroscopy, size-exclusion chromatography and GPC/MALLS. 71 ± 3% of fluorescence remained in the >5K MWCO fraction; this fraction showed a minor peak with a molecular mass (171 ± 11K) corresponding to injected glucan (~150K). Most excreted glucans were of lower molecular mass (13 ± 8.5K), indicating most (1→3)-β-D-glucans are excreted by the kidneys as smaller polysaccharides. The presence of urinary glucans may be an important indicator of fungal infection.
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Guthrie, Mackenzie L. "Toll Like Receptor 4 Stimulation Increases Scavenger Receptor A Expression On Murine Macrophages." Digital Commons @ East Tennessee State University, 2017. https://dc.etsu.edu/honors/418.
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Sepsis is the body’s response to an overwhelming infection and is a serious consequence of critical illness. It can cause tissue damage, organ failure, and death. Sepsis continues to have an unacceptably high mortality rate, due to the lack of effective treatments. Specific therapeutic targets for sepsis remain elusive since the complex functional changes that result in a septic state remain poorly understood. Macrophage Scavenger Receptor A (SRA, CD204) is a surface receptor that binds negatively charged, endogenous and exogenous ligands. We have discovered that SRA plays a significant role in the pathophysiology of sepsis. We have shown that mice with SRA have increased inflammation, decreased survival, and increased bacterial burden compared to SRA deficient mice. We have also found an increase in the expression of SRA on monocytes and macrophages in septic wild type mice. To determine the mechanism responsible for increased SRA expression in sepsis we treated a mouse macrophage cell line, (J774a.1), with mediators that stimulate toll like receptors (TLRs), innate immune receptors which are activated in sepsis. The cells were cultured with ultra pure LPS (a TLR 4 ligand), PAM3CSK4 (a TLR 2 ligand), glucan (a Dectin-1 ligand), ultra pure LPS and PAM3CSK4, or ultra pure LPS and glucan for 24 hours. The cells were stained with an SRA antibody, and flow cytometry was used to measure the SRA expression for each treatment group. LPS treatment alone resulted in a significant increase in SRA expression when compared to control cells. Specifically, LPS increased SRA expression by 53.4% compared to media alone (p
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Janakiraman, Vani. "Réponse immunitaire innée et adaptative pour des motifs moléculaire associés aux mycobactéries pathogènes (« PAMPs »)." Paris 6, 2010. http://www.theses.fr/2010PA066291.
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La tuberculose causée par Mycobacterium tuberculosis est la plus mortelle des maladies infectieuses. Les mycobactéries sont des pathogènes intra-cellulaires qui ont développé des mécanismes d’évasion spécifiques pour survivre au sein de leur hôte. Une réponse immune anti-mycobatérienne efficace met en jeu l’activation des cellules T CD4+ Th1 ainsi que la génération d’IFN- microbicide. Cependant, des patients ayant une tuberculose active présentent une réponse immune de type Th2 durant les stades les plus tardifs de l’infection. L’association de ce pathogène avec le VIH chez les patients atteints du SIDA et l’émergence de souches extrêmement résistantes aux traitements actuelles font de la tuberculose une « urgence mondiale ». Ainsi, découvrir les interactions moléculaires des motifs antigéniques associés aux mycobactéries pathogènes (« PAMPs ») avec le système immunitaire de l’hôte est important pour comprendre la pathogenèse de la tuberculose et pour permettre une immunointervention thérapeutique efficace. La mise en place d’une réponse immune contre M. Tuberulosis met en jeu l’interaction entre les systèmes immunitaires innés et adaptatifs. Les cellules de l’immunité innée comme les cellules dendritiques (CD) sont impliquées dans la reconnaissance du pathogène et des antigènes qui en dérives, dans la présentation de peptides antigéniques aux cellules T et dans la sécrétion d’un large panel de cytokines qui permettent la différenciation et l’expansion des cellules T CD4+ et T CD8+. Les cellules T CD4+ Th fournissent l’aide nécessaire aux lymphocytes B pour la production des anticorps. Outre la production d’anticorps, les cellules B peuvent aussi agir comme cellules présentatrices de l’antigène et produire différentes cytokines et chimiokines immunorégulatrices qui modulent la réponse immune et l’inflammation. Durant ma thèse, j’ai étudié l’interaction moléculaire des « PAMPs » de M. Tuberculosis avec des CD et des cellules B humaines et j’ai examiné in vivo les réponses immunes dirigées contre les « PAMPs » en association avec différentes molécules adjuvantes. Dans un premier temps, j’ai étudié la régulation des fonctions des CD humaines par un antigène mycobactérien de surface mannosylé : le mannose lipoarabinomannan (ManLAM). Le ManLAM est un composant principal de la membrane cellulaire des mycobactéries et est impliqué dans l’immunopathogenèse de la tuberculose. J’ai démontré que le ManLAM induisait la maturation des CD vers une réponse immune de type Th2 et la production de chimiokines impliquées dans la migration des cellules T Th2 et T régulatrice (Treg). De plus, les cellules B ont été retrouvées sur le site de réactions granulomateuses chez l’homme et la souris atteints de la tuberculose. Cependant le rôle des cellules B dans la réponse immune contre la tuberculose reste inconnu. A cet effet, j’ai étudié l’interaction du ManLAM avec des cellules B humaines issues de donneurs sains. J’ai démontré que le ManLAM stimulait la prolifération des cellules B avec une forte production d’IL-8 et d’IL-6. Mes résultats montrent de même que la prolifération des cellules B stimulées par le ManLAM avait pour origine l’interaction entre le ManLAM et le TLR-2. Ainsi, les cellules B éduquées par le ManLAM propagent la réponse immune de type Th2. L’ensemble de mes résultats démontrent que le ManLAM module la fonction des CD et des cellules B afin d’échapper à la réponse cellulaire T efficace contre M. Tuberculosis. PE, PPE sont de nouvelles familles de protéines qui ont été identifiées après que le génome de M. Tuberculosis ait été entièrement séquencé. Ces classes de protéines sont propres aux mycobactéries et la plupart d’entre elles sont des protéines de surface qui ont la capacité d’interagir avec les cellules du système immunitaire. J’ai étudié l’interaction de PE_PGRS 62 (Rv3812) avec les CD humaines et j’ai montré que PE_PGRS 62 agissait comme un ligant de TLR-2 et induisait la maturation des CD vers des réponses de type Th1. De plus, j’ai démontré que PE_PGRS 62 générait de fortes réponses immunitaires in vivo dans différents modèles expérimentaux. L’ensemble de ces résultats montre que PE_PGRS 62 met en place une réponse cellulaire de type Th1 en présence ou non d’antigènes immunorégulateurs tels que le ManLAM et la protéine gp120 du VIH. Ceci permet d’envisager l’utilisation de PE_PGRS 62 comme vaccin candidat pour combattre la tuberculose.
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Maurais, Luc. "Conception d’un procédé de microfabrication pour l’assemblage 3D puce-à-puce de circuits intégrés hétérogènes à des fins de prototypage." Mémoire, Université de Sherbrooke, 2018. http://hdl.handle.net/11143/11911.
Full textAbstract:
L’utilisation de photodiodes avalanche monophotoniques (PAMP) pour une utilisation au
sein d’imageur préclinique par tomographie d’émission par positrons est d’intérêt. En effet,
l’utilisation de ces photodétecteurs intégrés au CMOS est poussée par leurs excellentes
performances de résolution en temps ainsi que leur haute sensibilité. Cependant, l’utilisation
de ces détecteurs nécessite également un circuit intégré de contrôle visant à protéger
les photodiodes de courants trop élevés lors de déclenchement d’avalanches et de contrôler
leurs temps mort. Ces circuits de plus en plus sophistiqués nécessitent un espace significatif
diminuant ainsi la surface photosensible à la surface de la puce et diminuant leurs
sensibilités. L’assemblage 3D puce-à-puce est donc nécessaire dans le but d’augmenter la
surface photosensible et de ne pas limiter les fonctionnalités de contrôles électroniques
individuelles à chaque PAMP.
Ce document présente le développement d’un procédé d’assemblage 3D puce-à-puce visant
l’intégration de matrices de PAMP. Les étapes de microfabrication nécessaires visent l’intégration
d’interconnexions verticales au travers du substrat (TSV) permettant de transmettre
les signaux d’une couche à l’autre et le collage 3D de ceux-ci. De plus, des mesures
de caractéristiques de bruits ont été effectuées sur des puces ayant subi certaines étapes
de microfabrication du procédé d’assemblage 3D. Ces mesures ont été effectuées dans le
but de déterminer l’impact potentiel du procédé d’assemblage sur les performances des
PAMP intégrés en 3D.
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Darmoise, Alexandre F. "Lysosomal alpha-galactosidase A controls the generation of self lipid antigens for NKT cells." Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2011. http://dx.doi.org/10.18452/16292.
Full textAbstract:
CD1 Moleküle spielen eine wichtige Rolle in der Lipidpräsentation und T-Zell-Aktivierung. CD1d fungiert als Restriktionselement für NKT-Zellen, eine T-Zell-Untergruppe, die nach Erkennung von Glykosphingolipide (GSL), IFN-gamma und IL-4 produziert. NKT Zellen steuern folglich anschliessende Immunantworten. Den meisten infektiösen Mikroorganismen mangelt es jedoch an GSL-Antigenen zur Stimulation von NKT-Zellen. Der Wirtsorganismus hat daher einen Mechanismus entwickelt, der die Aktivierung der NKT-Zellen dennoch gewährleistet. NKT-Zellen erkennen auch endogene GSL, die in dendritischen Zellen (DZ) infolge von Toll-like-Rezeptor (TLR)-Stimulation durch Pathogene produziert werden. Bislang war unklar, wie genau TLR-Aktivierung zur Produktion von Selbst-GSL-Antigenen führt. Ziel dieser Arbeit war es die Verknüpfung der beiden Prozesse aufzudecken. Diese Dissertation zeigt, dass alpha-Galaktosidase A (a-Gal A) als lysosomales Schlüsselenzym für den konstitutiven Abbau von Selbst-GSL-Antigenen in DZ fungiert. NKT-Zellen antworteten auf CD1d-restringierte Antigene, die von DZ, denen a-Gal A-Aktivität fehlte, präsentiert wurden. Ferner expandierten NKT-Zellen nach adoptiven Transfer in a-Gal A-defiziente Mäuse in Abhängigkeit von CD1d-Expression im Wirtsorganismus. Diese Arbeit zeigte auch, wie GSL-Antigene dem Abbau durch a-Gal A entkommen und für die NKT-Zell-Aktivierung bei Infektionen verfügbar werden. Unter normalen Bedingungen wurden die GSL durch a-Gal A abgebaut. TLR-vermittelte Signale führten jedoch zu Inhibierung der a-Gal A-Aktivität in DZ und resultierten somit in einer GSL-Akkumulation in den Lysosomen. Wir identifizierten einen neuen Regulationsmechanismus der NKT-Zell-Aktivierung bei Infektionen, der auf der Induktion von lysosomalen GSL-Antigenen durch TLR-vermittelte Hemmung der a-Gal A-Aktivität beruht. Diese Dissertation beantwortet fundamentale Fragen der NKT-Zell-Biologie und ebnet den Weg dieses System für therapeutische Ansätze zu nutzen.CD1 molecules are pivotal for lipid presentation to T lymphocytes. Notably, CD1d functions as a restriction element for NKT cells, a T-cell lineage that produces IFN-gamma and IL-4 following recognition of glycosphingolipids (GSL). Consequently, NKT cells exert decisive regulatory functions on downstream immune responses. Most microbes potentially causing infection of the host lack GSL antigens to stimulate NKT cells. However, facing this challenge, the host developed a mechanism to ensure NKT-cell activation. This pathway exploits the property of NKT cells to react with self GSLs produced in dendritic cells (DCs) stimulated by pathogens through Toll-like receptors (TLR). How TLR engagement leads to production of self GSL antigens remains elusive. The aim of this study was to provide a mechanistic link between these two processes. Here, we identified alpha-galactosidase A (a-Gal A) as a key lysosomal enzyme required for constitutive degradation of self GSL antigens in DCs. Accordingly, NKT cells exposed to DCs lacking a-Gal A activity were activated in the context of CD1d-presented antigens. In addition, NKT cells underwent robust expansion upon transfer to a-Gal A-deficient mice that required CD1d expression by the host. This study further addressed the critical question as to how GSL antigens escape degradation by a-Gal A, and thus become available for presentation to NKT cells in infection. Accordingly, we found that TLR signaling targeted a-Gal A activity for negative regulation in DCs. Consequently, GSLs degraded by a-Gal A in steady-state conditions were induced in lysosomes. Based on these findings, we propose a new pathway that warrants the activation of NKT cells in infection by self GSL antigens induced through TLR-mediated inhibition of a-Gal A activity. Overall, this dissertation answers fundamental questions in the NKT field, and paves the way toward exploring this antigen presentation axis for therapeutic use.
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Lemaire, William. "Conception d’un circuit de lecture à étampes temporelles multiples pour un photodétecteur destiné à la tomographie d’émission par positrons." Mémoire, Université de Sherbrooke, 2018. http://hdl.handle.net/11143/11814.
Full textAbstract:
La médecine moderne fait usage de divers appareils pour faciliter le diagnostic et le traitement des maladies. Parmi ceux-ci, l’imagerie par tomographie d’émission par positrons (TEP) se démarque par sa capacité d’imager des processus biologiques spécifiques comme le métabolisme du glucose. Cette caractéristique permet de mettre en évidence des signes distinctifs des maladies comme le cancer à l’aide de radiotraceurs capables de cibler certaines cellules. Dans le but de favoriser de meilleurs diagnostics et de mener des recherches de pointe dans le domaine médical, la qualité des images produites par les appareils TEP doit être améliorée. Les avancées des dernières années ont permis d’améliorer la résolution spatiale des images jusqu’à pratiquement atteindre la limite théorique imposée par le déplacement du positron lors du processus de désintégration. Depuis, les travaux s’orientent plutôt vers l’amélioration du contraste de l’image en intégrant la mesure du temps de vol (TdV) dans l’algorithme de reconstruction. Le défi dans cette mesure réside dans la conception d’un photodétecteur avec une résolution temporelle suffisante pour localiser le lieu d’émission du radiotraceur entre deux détecteurs coïncidents. La plupart des photodétecteurs actuels utilisent un seuil sur le nombre de photons de scintillation observé pour déterminer le temps d’arrivée des photons d’annihilation dans le scintillateur. Cependant, plusieurs travaux ont démontré qu’une meilleure résolution temporelle est atteignable en pondérant adéquatement l’information temporelle numérisée de plusieurs photons de scintillation à la place de n’en considérer qu’un seul. Dans le but d’améliorer la résolution temporelle des photodétecteurs, l’utilisation d’un estimateur statistique combinant l’information de plusieurs photons de scintillation se révèle une méthode prometteuse en considérant les résultats théoriques. Cependant, une implémentation matérielle pouvant être intégrée à un appareil TEP reste à être démontrée. Les travaux de recherche présentés dans ce mémoire portent sur l’intégration d’un tel estimateur statistique à un photodétecteur pour la TEP. Ces travaux ont mené au développement d’une chaine d’acquisition qui comporte 1) un circuit de lecture, 2) une trieuse, 3) un filtre de bruit thermique et 4) un estimateur statistique du temps d’interaction basé sur le Best Linear Unbiased Estimator (BLUE). L’intégration de cette chaine à même le circuit intégré du photodétecteur de 1 x 1 mm2 en CMOS 65 nm permet de réduire la bande passante de 250 Mbit/s à 0,5 Mbit/s et le temps mort de 68,6 μs à 1024 ns. Des simulations démontrent l’atteinte d’une résolution temporelle qui s’approche de la limite inférieure théorique (appelée borne de Cramér-Rao) quant à la résolution temporelle atteignable par ce photodétecteur.
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Boisvert, Alexandre. "Conception d'un circuit d'étouffement pour photodiodes à avalanche en mode Geiger pour intégration hétérogène 3D." Mémoire, Université de Sherbrooke, 2014. http://hdl.handle.net/11143/6153.
Full textAbstract:
Le Groupe de Recherche en Appareillage Médical de Sherbrooke (GRAMS) travaille actuellement sur un programme de recherche portant sur des photodiodes à avalanche monophotoniques (PAMP) opérées en mode Geiger en vue d'une application à la tomographie d’émission par positrons (TEP). Pour opérer dans ce mode, la PAMP, ou SPAD selon l’acronyme anglais (Single Photon Avalanche Diode), requiert un circuit d'étouffement (CE) pour, d’une part, arrêter l’avalanche pouvant causer sa destruction et, d’autre part, la réinitialiser en mode d’attente d’un nouveau photon. Le rôle de ce CE comprend également une électronique de communication vers les étages de traitement avancé de signaux. La performance temporelle optimale du CE est réalisée lorsqu’il est juxtaposé à la PAMP. Cependant, cela entraîne une réduction de la surface photosensible ; un élément crucial en imagerie. L’intégration 3D, à base d'interconnexions verticales, offr une solution élégante et performante à cette problématique par l’empilement de circuits intégrés possédant différentes fonctions (PAMP, CE et traitement avancé de signaux). Dans l’approche proposée, des circuits d’étouffement de 50 [mu]m x 50 [mu]m réalisés sur une technologie CMOS 130 nm 3D Tezzaron, contenant chacun 112 transistors, sont matricés afin de correspondre à une matrice de PAMP localisée sur une couche électronique supérieure. Chaque circuit d'étouffement possède une gigue temporelle de 7,47 ps RMS selon des simulations faites avec le logiciel Cadence. Le CE a la flexibilité d'ajuster les temps d'étouffement et de recharge pour la PAMP tout en présentant une faible consommation de puissance ( ~ 0,33 mW à 33 Mcps). La conception du PAMP nécessite de supporter des tensions supérieures aux 3,3 V de la technologie. Pour répondre à ce problème, des transistors à drain étendu (DEMOS) ont été réalisés. En raison de retards de production par les fabricants, les circuits n’ont pu être testés physiquement par des mesures. Les résultats de ce mémoire sont par conséquent basés sur des résultats de simulations avec le logiciel Cadence.
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Inbarajan, Prabhu Anand. "PAMPA II Advanced Charting System." Thesis, Texas A&M University, 2003. http://hdl.handle.net/1969.1/387.
Full textAbstract:
Project Management is the primary key to successful software development. In 1995 Caper Jones stated that the failure or cancellation rate of large software systems was over 20% in his article on patterns of large software systems. More than two thirds of the projects fail due to improper management of skills, activities, and personnel. One main reason is that software is not a tangible entity and is hard to visualize and hence to monitor. A manager has to be skilled in different CASE tools and technologies to track and manage a software development process successfully. The volume of results produced by these CASE tools is so huge that a high level manager cannot look into all the details. He has to get a high level picture of the project, to know where the project is heading, and if needed, then look into the finer level details by drilling down to locate and correct problems. The objective of this thesis is to build an Advanced Charting System (ACS), which would act as a companion to PAMPA 2 (Project Attribute Monitoring and Prediction Associate) and help a manager visualize the state of a software project over a standard World Wide Web browser. The PAMPA 2 ACS will be responsible for visualizing and tracking of resources, tasks, schedules and milestones of a software project described in the plan. PAMPA 2 ACS will have the ability to depict the status of the project through a variety of graphs and charts. PAMPA 2 ACS implements a novel charting technique called as DOT Chart to track the processes and activities of a software project. PAMPA 2 ACS provides a multilevel view of the project status. PAMPA 2 ACS will be able to track any arbitrary plan starting from a collapsed / concise view of a whole project. This can be further drilled down to the lowest level of detail. The status can be viewed at the project version level, plan and workbreakdown levels, process, sub process, and activity level. Among all the process models, the DOT charts can be applied effectively to spiral process model where each spiral represents a project version.
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Navarro, Serer Judith 1990. "Understanding functional interplay between PARP-1 and PARP-2 in T cell development and function." Doctoral thesis, Universitat Pompeu Fabra, 2016. http://hdl.handle.net/10803/481994.
Full textAbstract:
T-cell homeostasis must be tightly regulated and maintained in order to guarantee appropriate immune responses and prevent immunopathology. This maintenance depends on MHC-TCR interaction and cytokine-mediated signals among others. However, cell intrinsic factors that modulate essential functions in T-cells must be also integrated to support genomic stability and contribute to the control of T-cell homeostasis.
The present work establishes a coordinated role of poly (ADP-ribose) polymerase-1 (PARP-1) and PARP-2 in maintaining T-lymphocyte number and function, demonstrated by the defective thymocyte maturation and diminished numbers of peripheral CD4+ and CD8+ T cells in mice bearing a T-cell specific deletion of PARP-2 in a PARP-1-deficient background. Moreover, this T-cell lymphopenia is associated with an increased DNA-damage and concomitant cell death, leading to highly aggressive spontaneous T-cell lymphomas in PARP-1/PARP-2 double-deficient mice.
Our findings highlight the importance of understanding the specific involvement of both proteins in key biological processes that could have an impact on the development and exploitation of PARP-inhibitors.L’homeòstasi de la cèl·lula T ha d’estar estrictament regulada per tal de garantir una correcta resposta immunitària i prevenir alhora qualsevol problema immunopatològic. Aquest correcte manteniment depèn, entre d’altres, de la interacció amb el complex MHC-TCR i de les senyals de diferents interleuquines. No obstant, hi ha altres factors intrínsecs que intervenen en la modulació de les funcions vitals de la cèl·lula T i que han d’estar també correctament integrats en tot el sistema per tal de garantir una correcta estabilitat genòmica i contribuir en el control de l’homeòstasi de la cèl·lula T. El present treball estableix el paper coordinat entre els enzims poli (ADP-ribosa) polimerasa-1 (PARP-1) i PARP-2 en el manteniment del nombre i la funció dels limfòcits T, tal i com es demostra amb el defecte en maduració i el descens en el número de cèl·lules CD4+ i CD8+ perifèriques que tenen els ratolins amb deleció de PARP-2 en un background PARP-1 deficient. A més a més, aquesta limfopènia està associada amb un increment del dany en el ADN i una concomitant mort cel·lular, que condueix al desenvolupament espontani de limfomes T molt agressius en els ratolins dobles deficients per PARP-1 i PARP-2. Els nostres resultats posen de manifest la importància de conèixer correctament el paper específic de les dues proteïnes en processos biològics rellevants, ja que podria tenir especial impacte en el desenvolupament i l’explotació dels inhibidors PARP.
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Patrocínio, Dennis Nogarolli Marques. "O povo do pampa : uma história de vida em meio aos campos nativos do bioma pampa." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2015. http://hdl.handle.net/10183/132903.
Full textAbstract:
Criar gado em campo nativo é uma prática que, historicamente, é desenvolvida no Estado do Rio Grande do Sul. Desde a preação do gado xucro distribuído pelas vastas planícies do bioma pampa até a produção de gado em estâncias, encontramos os elementos que configuraram a formação política e cultural do Estado. Anteriormente, em um passado ainda mais distante, povos de várias etnias passaram por esses ambientes, deixando costumes que, mesmo que se tenham passado séculos de intervenções culturais, ainda podem ser observados permeando a cultura do povo do Pampa. Em meio a esse ambiente, o presente estudo tem como objetivo identificar e visibilizar determinadas práticas, a relação com o ambiente e alguns dos aspectos simbólicos que envolvem os “pequenos produtores rurais” que criam gado em campo nativo, os quais são denominados de pecuaristas familiares. Para isso, foi realizado um resgate da formação do ambiente, até a chegada dos colonizadores, de modo a identificar os principais momentos históricos que se entremeiam para formar esse bioma como o conhecemos hoje. A história recente será contada com o apoio de uma família de pecuaristas familiares inserida na Serra do Caverá, localidade pertencente ao município de Rosário do Sul – RS. É em meio à singularidade da Serra do Caverá – entre cerros e coxilhas - que, fazendo uso da abordagem etnográfica, apresentarei a história de vida dessa família. Caracterizá-los, de modo a identificar valores intrínsecos à prática de criação de gado em campo nativo, suas relações com o entorno da propriedade e com o ambiente do qual fazem parte, permite reconhecer e valorizar uma prática secular de produção de gado. Percebe-se que esses pecuaristas familiares, com seu modo de fazer pecuária, mantêm uma relação estreita com os elementos da biodiversidade que o compõem, mas, por outro lado, nota-se que as políticas públicas de apoio à pecuária familiar, no contexto do bioma Pampa, são escassas, o que determinou, até pouco tempo, que estes tenham se tornado invisíveis ao Estado. Assim, somando a esses fatores a necessidade de identificar os valores simbólicos inerentes ao modo de se fazer pecuária na localidade e, sobretudo, à família pesquisada, concluímos que estes são indissociáveis ao ambiente que os cerca, ficando perceptível a premência de identificar e ampliar o conhecimento dessas práticas e sua aliança para a conservação da biodiversidade no bioma Pampa, para aí, sim, traçar estratégias de conservação que aliem o elemento humano com a conservação, pois, além de utilizar o campo nativo como insumo à produção, esse público de pecuaristas mantém a guarda do ambiente.Raising cattle on natural pasture is a historical practice in Rio Grande do Sul. From the wild cattle hunt spread throughout the vast plains of Pampas biome to cattle production in ranches, we find elements that shaped the political and cultural structure of the state. In a remote past, people from various ethnic groups passed through these environments introducing traditions which, even after centuries of cultural interventions, can still be observed permeating the culture of people from Pampa. This study aims to identify and disclose some practices, their relation with the environment and some of the symbolic aspects regarding “small rural producers” that raise cattle on natural pasture, who are called family farmers. For this purpose, a research on the development of the environment up to the arrival of settlers was held in order to identify key historical moments that formed this biome as we know it today. The recent history will be narrated with the support of a family farmer from Serra do Caverá, a locality in Rosario do Sul county, Rio Grande do Sul. Amid the uniqueness of Serra do Caverá landscape I will present the life story of this family using the ethnographic approach. Characterizing this family in order to identify intrinsic values of livestock on natural pasture, their relation with the surroundings of the property and also with the environment to which they belong, enable us to value an ancient practice of livestock production. Family farmers keep a close relationship with the elements that constitute the environment biodiversity; on the other hand, public policies to support family farming of Pampa biome are limited, which led these families to become invisible to the state up until recently. Therefore, it is clear the urgency to identify and expand the knowledge of livestock practice and its role in the conservation of biodiversity in Pampa biome in order to design strategies that combine the human element and conservation, as these farmers use natural pasture as an input to production besides taking care of the environment.
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Sartorio, Carolina. "PAP-Style Cases." J PHILOSOPHY INC, 2016. http://hdl.handle.net/10150/625953.
Full textAbstract:
Over the years, two models of freedom have emerged as competitors: the alternative-possibilities model, which states that acting freely consists (at least partly) in being able to do otherwise, and, more recently, the actual-sequence model, which states that acting freely is exclusively a function of the actual sequence of events issuing in our behavior. In general, a natural strategy when trying to decide between two models of a certain concept is to look for examples that support one model and undermine the other. Frankfurt-style cases have been used for this kind of purpose, to challenge the alternative-possibilities view and support the actual-sequence view. In this paper I examine the prospects of the counterparts of Frankfurt-style cases: “PAP-style” cases, or cases that could be used to support the alternative-possibilities view and challenge the actual-sequence view. I argue that there are no successful PAP-style cases.
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Sotelo, Juan Manuel. "Estructura metálica-Quemú Quemú-La Pampa." Bachelor's thesis, Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales, 2015. http://hdl.handle.net/11086/1879.
Full textAbstract:
Práctica Supervisada (IC)--FCEFN-UNC, 2015Evalúa una estructura metálica la cual ya estaba diseñada y sus partes estructurales ya estaban construidas (Columnas, arcos, montantes, etc.). Al estar ya construidos se relevaron estos elementos. En caso de no verificar se propusieron refuerzos a las estructuras, para hacer posible que todos los elementos estén acordes a lo exigido por los reglamentos. Despues de esto teniendo en cuenta el estudio de suelo se propuso un sistema de fundaciones y se lo diseño
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Skoglund, Anders. "Multivariate modelling and monitoring for stabilisation of paperboard manufacturing /." Linköping : Univ, 2004. http://www.bibl.liu.se/liupubl/disp/disp2004/tek903s.pdf.
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Chumble, Anuja. "Epigenetic Alterations of Toll-Like Receptors by TET2 in Spontaneous Preterm Labor." VCU Scholars Compass, 2014. http://scholarscompass.vcu.edu/etd/3469.
Full textAbstract:
Increasing evidence implicates the presence of bacteria in intrauterine tissues as an important risk factor for spontaneous preterm labor. Epigenetic alterations of innate immunity genes may increase the mother’s sensitivity to subclinical levels of bacteria. This study examined the presence of TET2, TLR-2, and TLR-9 in intrauterine tissue, and evaluated whether epigenetic alterations of these genes, as well as IL-8, changed their expression in human decidual tissue and a macrophage cell culture. Immunohistochemicalstaining was used to detect the presence of these proteins in intrauterine tissue. Gene expression changes were evaluated in stimulated monocytes and macrophages. Fluorescence immunohistochemistry was used to track translocation of TET2 in stimulated monocytes and macrophages. Secreted IL-8 concentration was detected with ELISA. Decidual expression of TET2, TLR-2, and TLR-9 increased in the order TNL < TL < sPTL < iPTL. This study found that TET2, TLR-2, TLR-9, and IL-8 are regulated by epigenetic mechanisms. This study was the first to report activation of TET2 involves its translocation from the cytosol to the nucleus in macrophages.
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Boudra, Mohammed-Tayyib. "Facteurs modulant la radiosensibilité : rôle des protéines PARP-1, PARP-2 et Cdk5 et implication de la chromatine." Phd thesis, Université Paris Sud - Paris XI, 2011. http://tel.archives-ouvertes.fr/tel-00662941.
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Les modifications post-traductionnelles des protéines de réparation de l'ADN et des facteurs chromatiniens par poly(ADP-ribose)ylation et par phosphorylation sont essentielles pour le maintien de l'intégrité de l'ADN et de la chromatine, en particulier dans la réponse cellulaire aux dommages de l'ADN induits par radiation ionisantes (RI). Parmi les protéines impliquées dans ces deux processus nous trouvons, respectivement, la poly(ADP-ribose) polymérase-1 (PARP-1) et PARP-2, et la kinase dépendante des cyclines Cdk5 : PARP-1 et PARP-2 sont impliqué dans le mécanisme de réparationdes cassures simples brin (CSBs) de l'ADN (Single Strand Break Repair : SSBR ) et la déplétion de Cdk5 a été liée à l'augmentation de la sensibilité des cellules aux inhibiteurs de PARPs. Nous avons montré, en utilisant des cellules HeLa stablement déplété pour Cdk5 ou PARP-2, que ces deux protéines sont impliquées dans les deux sous-voies du SSBR, le short- (SPR) et le long-patch repair (LPR). L'absence de Cdk5 ou PARP-2 entraîne des modifications du fonctionnement du SSBR, notamment en termes de recrutement des protéines de réparation PARP-1 et XRCC1, impliquées dans le SPR, et PCNA, protéine clé du LPR, au site du photo-dommage. PARP-2 et Cdk5 agissent aussi sur la balance du niveau des poly(ADP-ribose) car en absence de Cdk5 une hyper-activation de PARP-1 a été montrée, et en absence de PARP-2 une diminution de l'activité de la protéine poly(ADP-ribose) glycohydrolase (PARG) a été aussi observée. Cependant, malgré ces changements les deux lignées cellulaires dépourvues de Cdk5 (Cdk5KD) ou de PARP-2 (PARP-2KD) réparent de façon normale les CSBs radio-induites, mais, intéressement et contrairement aux cellules PARP-2KD, les cellules Cdk5KDsont sensibles à l'effet létal des RI. De plus nous avons montré que Cdk5, PARP-2 et PARG sont toutes les trois impliquées dans la régulation du recrutement et de dissociation du facteur chromatinien ALC1 suggérant leur implication dans la régulation de la dynamique de la chromatine en réponse aux photo-dommages de l'ADN. Ces résultats avec l'observation de la diminution du recrutement de PARP-1 dans les cellules Cdk5KD et PARP-2KD, montrent l'apparition d'un réseau complexe de phosphorylation et de poly(ADP-ribose)ylation en réponse aux RI qui implique Cdk5 , PARP-1,PARP-2 and PARG et qui est fort probablement initié par l'activité kinase de Cdk5.
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Düll, Fabian [Verfasser], Christian [Akademischer Betreuer] Papp, Christian [Gutachter] Papp, and Jörg [Gutachter] Libuda. "Metal Nanocluster Arrays as Model System for Catalysts / Fabian Düll ; Gutachter: Christian Papp, Jörg Libuda ; Betreuer: Christian Papp." Erlangen : Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 2019. http://d-nb.info/1202146015/34.
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Ahmed, Zina. "Poly-ADP ribos polymeras (PARP) inhibitorers effekt på bröstcancer : Poly-ADP ribos polymeras (PARP) inhibitorers effekt på bröstcancer." Thesis, Umeå universitet, Kemiska institutionen, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-103397.
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Muñoz, Frances M. "Calcium Modulation of PARP-mediated Cell Death." Diss., The University of Arizona, 2015. http://hdl.handle.net/10150/347337.
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Many pathological conditions, including renal disease, are associated with oxidative stress. 2,3,5-tris(Glutathion-S-yl)hydroquinone (TGHQ), a potent nephrotoxic and nephrocarcinogenic metabolite of benzene and hydroquinone, generates reactive oxygen species (ROS), can cause DNA strand breaks, and the subsequent activation of DNA repair proteins, including poly(ADP-ribose) polymerase (PARP)-1. Under robust oxidative damage, PARP-1 is hyper-activated, which causes elevations in intracellular calcium concentrations (iCa²⁺), NAD⁺ and ATP depletion, and ultimately necrotic cell death. The role of Ca²⁺ in PARP-dependent necrotic cell death remains unclear. We therefore sought to determine the relationship between Ca²⁺ and PARP-1 during TGHQ-induced necrotic cell death in human renal proximal tubule epithelial cells (HK-2). Extracellular Ca²⁺ is responsible for coupling PARP-1 activation to increases in iCa²⁺ during TGHQ-induced cell death. Moreover, organelles such as the endoplasmic reticulum and the mitochondria, which contain intracellular Ca²⁺ stores play no role in increases of iCa²⁺. PARP-1 inhibition attenuates increases in iCa²⁺ induced by TGHQ, and treatment with 2-aminoethoxydiphenyl borate (2-APB), a store-operated Ca²⁺ channel (SOC) inhibitor, restored cell viability, levels of NAD⁺, and attenuated PAR protein-ribosylation (PARylation). Concurrent with SOC activation having a direct effect on PARP-1 activity, and PARP-1 inhibition attenuating increases in iCa²⁺, the results suggest that PARP-1 and SOCs are coupled during TGHQ-induced cell death. We also explored the relationship between SOC activation and PARP-1 downstream of PARP-1 activity. Poly(ADP-ribose)glycohydrolase (PARG), which catalyzes the degradation of PARs to yield free ADP-ribose (ADPR), is known to activate SOCs. Interestingly, siRNA knockdown of PARG modestly increased PAR ribosylation, but did not restore cell viability in the presence of TGHQ, indicating that free ADPR is not responsible for SOC activation in HK-2 cells. Overall, our results suggest that PARP-1 and Ca²⁺ are coupled through SOC entry, and that this relationship may involve alternative PAR-mediated signaling that leads to necrotic cell death. To further elucidate the role of PAR polymers in response to TGHQ, we determined the cellular co-localization of PAR by immunofluorescent staining. PAR polymers originally co-localized in the nucleus, and in the cytosol at later time points. Immunoprecipitation with a pADPr antibody and further analysis via mass spectrometry revealed PARylation of many stress-related proteins and Ca²⁺-related proteins upon TGHQ treatment. We therefore speculate that cytosolic PAR may cause downstream signaling, PARylating proteins that activate store-operated Ca²⁺ entry either directly through Ca²⁺-related proteins or PARylation of stress-related proteins. Thus, PARylation of proteins may contribute to increases in iCa²⁺ concentrations, leading to PARP-1-dependent necrotic cell death. Our studies provide new insight into PARP-mediated necrotic cell death. Ca²⁺ is coupled to PARP-1 hyperactivation through SOCs, where iCa²⁺ increases are independent of PARG activity, demonstrating a novel signaling pathway for PARP-dependent necrotic cell death.
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Gittens, William. "PARP/XRCC1 surveillance of the human genome." Thesis, University of Sussex, 2018. http://sro.sussex.ac.uk/id/eprint/76255/.
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DNA single strand breaks (SSBs) are one of the most common lesions to genomic DNA, arising from various endogenous and exogenous sources. Single strand break repair (SSBR) constitutes a biochemical pathway whereby SSBs are detected, enzymatically processed and ligated. Whilst the general mechanisms of SSBR are relatively well described in vitro, there are remaining questions concerning how the pathway operates in vivo. For example, an early step in SSBR is thought to be the poly(ADP-ribose) polymerase (PARP)-dependent modification of SSB-proximal proteins with ADP-ribose, which is a signal for the recruitment of downstream repair factors, including the central scaffold XRCC1. Yet, the presence of multiple DNA-dependent PARP genes (PARP1, PARP2 and PARP3) has caused confusion regarding their specific roles in SSBR. This thesis potentially clarifies some contentious aspects of PARP function in the repair of SSBs induced by reactive oxygen species (ROS) and by Topoisomerase 1 (Top1). By employing PARP1-/-/PARP2-/- cells generated herein using CRISPR-Cas9 technology, in combination with preextraction immunofluorescence imaging and high-content analysis, I demonstrate that both PARP1 and PARP2 contribute towards ROS-induced ADP-ribosylation and XRCC1 chromatin-localization, but that in response to Top1-SSBs, these functions are specifically supported by PARP1 alone. Furthermore, using TDP1-/- and XRCC1-/-/TDP1-/- cells also generated herein, I characterize a striking hyper-ADP-ribosylation phenotype in response to Top1-SSBs. The clinical significance of this was confirmed by co-workers, who observed a similar phenotype in an XRCC1-deficient patient, where mutations in XRCC1 underlie a novel cerebellar neurodegenerative disease. This phenotype could be utilized in future to screen for genes with novel functions in SSBR. Finally, I investigate the functional implications of disrupted SSBR genes for rates of repair and cellular viability using alkaline single-cell electrophoresis and clonogenic survival assay. In doing so, I unexpectedly discovered that deletion of PARP1 suppresses CPT-induced comet tail moments of WT and XRCC1-/- cells.
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Cisneros, Luis Jaime. "Osear G. Pamo Reyna, Medicina y lenguaje." Pontificia Universidad Católica del Perú, 2013. http://repositorio.pucp.edu.pe/index/handle/123456789/101227.
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Vieira, Osvaldo Arthur Menezes. "Simões Lopes Neto : uma Salomé no pampa." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2006. http://hdl.handle.net/10183/11390.
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Este trabalho tem por finalidade analisar a representação mítica de Salomé e suas ressonâncias na obra de Simões Lopes Neto e defender a idéia de que o autor, ao reler o mito, ambientando-o nos pampas do Rio Grande, transcende o mero pitoresco e a mera cor local, colocando-os a serviço da releitura desse mito. É objetivo principal deste estudo, portanto, ver nessa releitura um dos elementos responsáveis por tal transcendência. A fim de qualificar o estudo, são feitas uma reflexão sobre mito e literatura e uma investigação sobre a Salomé histórica, bem como as suas releituras. A análise dos contos Cabelos da china, Jogo do osso, No manantial, Contrabandista e O Negro Bonifácio, de Contos Gauchescos, e da obra Cancioneiro Guasca permite constatar nas personagens femininas dos referidos textos elementos que comprovam a releitura do mito de Salomé.Este trabajo tiene por finalidad analizar la representación mítica de Salomé y sus resonancias en la obra de Simões Lopes Neto y defender la idea de que el autor, al releer el mito, ambientandolo en las pampas de Rio Grande, transciende lo pintoresco y el simple color local, poniendolos a servicio de la relectura del mito. Es objetivo principal de este estúdio, por lo tanto, ver en esta relectura uno de los elementos responsables por tal transcendencia. A fin de calificar el estúdio, son hechas una reflexión sobre mito y literatura y una investigación sobre la Salomé histórica, así como sus relecturas. El análisis de los cuentos Cabelos da china, Jogo do osso, No manantial, Contrabandista y O Negro Bonifácio, de Contos Gauchescos, y de la obra Cancioneiro Guasca permite constatar en los personajes femeninos de los referidos textos elementos que comprueban la relectura del mito de Salomé.
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Bedoya, Nadramia Melissa. "Soray pampa hotel y refugios de montaña." Bachelor's thesis, Universidad Peruana de Ciencias Aplicadas (UPC), 2013. http://hdl.handle.net/10757/273344.
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El presente proyecto de tesis trata sobre la construcción del hotel “Soray Pampa” en Cusco, un hotel de montaña 5 estrellas que será el punto de partida hacia una cadena de refugios de categoría internacional a través de las rutas Soray PampaMachu Picchu y Soray Pampa-Choquequirau. Los capítulos de la tesis abarcan diversos temas, tales como: los aspectos turísticos en el Perú, la relación entre la arquitectura y el turismo, la importancia turística de la zona del Cusco, el análisis del usuario, el estudio del terreno, la arquitectura bioclimática, el manejo del paisaje, los materiales utilizados, el programa del hotel, el proceso de diseño, etc. Con la construcción de este hotel se pretende crear un nuevo tipo de turismo en el Perú, que combine el confort con la naturaleza y la aventura outdoor. Este proyecto permitirá dar a conocer al mundo parte de los maravillosos lugares con los que cuenta el país, pero que debido a la falta de infraestructura y de planes de desarrollo turístico no son visitados aún. Además, constituye un claro ejemplo de cómo las poblaciones más necesitadas de las zonas alejadas se pueden beneficiar del turismo y aprovecharlo como una herramienta para el desarrollo.Tesis